Remember, cracking a second egg that you don't need just gives you more to clean up afterward. Go break some eggs.
👀 The Read
“Two Species” isn’t the rule you think it is.
Not every nonclinical program needs a rodent and a nonrodent.
The reflex is automatic: one rodent, one nonrodent, every program. Two species or it isn't a real tox package.
That default is real — for a conventional molecule. But it is not universal, and treating it as universal costs money, animals, and sometimes your IND.
Here's where the default comes from. For a conventional molecule, general toxicity is assessed in one rodent and one nonrodent, because you can't predict up front which organ systems will matter and the two species catch different things. This comes from the Thalidomide debacle many years ago.
Sensible…but the moment your program stops being a conventional molecule, you have to start thinking bigger.
→ For example, in biologics, species selection is driven by pharmacological relevance, not by counting to two. The animal has to express the target and show the relevant pharmacology — otherwise you're dosing a species your drug doesn't meaningfully act on, the data becomes noise, and you are wasting animals. If only one species is pharmacologically relevant, you run one. If none of the standard species is relevant, two won't save you — you need a homologous molecule or a transgenic model instead.
→ Relevance cuts the same way for other molecule types as well. A second species that doesn't recapitulate human-relevant biology doesn't add rigor; it adds findings you then have to explain, some with nothing to do with humans. ADCs, nanoparticles, ocular compounds — these all have to be scientifically investigated to understand what the best toxicology program would look like for that molecule.
→ And when you're building on existing data — a 505(b)(2), a reference-listed drug, a prior program — you're bridging, not rebuilding. Repeating a full two-species program you could have referenced is spend with no return.
So the question was never "did you run two species?" It's "is each species you ran actually relevant to your compound?"
Two irrelevant species could show less than one relevant one, and trying to explain that in your regulatory narrative may result in more time, money and headaches to get to the clinic.
The Misconception: Every IND-enabling program requires two species — a rodent and a nonrodent.
The Correction: Two species is the default for conventional molecules, but it’s not a universal rule. Different molecule types require different levels of “species rigor”, and understanding which one you need comes down to understanding the scientific foundation of your compound.
📜 The full course syllabus, at your fingertips
If you didn’t know, I built a course called The Complete Guide to Nonclinical Development. I always put course previews on LinkedIn and little tidbits in my newsletters, but here’s a full view of what’s actually in it — all 12+ modules.
Click the card below to see all the lessons within each module:
